• Journal of Pharmacopuncture
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• v.19 no.3
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• pp.253-258
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• 2016

Objectives: The goals of this research were to evaluate acute (single-dose) and sub-acute (repeated-dose) toxicity profiles of methanolic extract of Pistacia integerrima J. L. Stewart ex Brandis (PI) for Wistar rats and to assess the safety profile of PI by observing physiological changes, mortality, changes in body weight, the histopathology of body organs, the hematology and the biochemistry of the animals. Methods: The toxicity profile of PI was evaluated using Wistar rats of both sexes. Animals were divided into four groups: Group 1; control group (normal saline), Group 2; PI-1 (250 mg/kg), Group 3; PI-2 (500 mg/kg), Group 4; PL-3 (1,000 mg/kg). An acute-toxicity study in which animals received a single dose of PI extract (2,000 mg/kg) and were then observed for 14 days for changes in skin, fur, eye color, mucous membrane secretions and excretions, gait, posture, and tonic or clonic movements was performed according to guideline 425 of the Organization of Economic and Corporation Development (OECD). In the repeated-dose toxicity study (OECD - 407) animals received a daily dose of PI extract for 28 days (4 weeks). The parameters observed in this study include body weight, hematology and biochemistry of the animals. Results: In the acute toxicity study, no mortalities or changes in behavior were noted in the animals. The repeated-dose toxicity study was also devoid of any toxicity in the animals during the 28 days of testing with PI extract. The extract did not alter- the body weight, hematology or biochemistry of the animals. The methanolic extract of PI was to be found safe to the no-observed-adverse-effect-level (NOAEL) for the single-dose and repeated-dose toxicity tests in rats. Conclusion: The methanolic extract of PI was devoid of toxicity; hence, it can be used for various ayurvedic preparations and treatments of diseases.

• The Korean Journal of Community Living Science
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• v.26 no.3
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• pp.511-522
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• 2015

This study investigates the acute and repeated-dose oral toxicity of crude antifungal compounds produced by Lactobacillus plantarum AF1 (Lb. plantarum AF1) and Lactobacillus plantarum HD1 (Lb. plantarum HD1) in male and female Sprague Dawley rats. In the acute toxicity study, crude antifungal compounds (500, 1,000, and 2,000 mg/kg) did not reduce mortality or produce significant changes in general behaviors or the gross appearance of external and internal organs. In the repeated-dose toxicity study, crude antifungal compounds were administered orally to rats at doses of 500, 1,000, and 2,000 mg/kg daily for 28 days. There were no test-article-related deaths, abnormal clinical signs, or body weight changes. In addition, there were no significant differences between groups treated with crude antifungal compounds and the control group in their organ weight, hematological and serum biochemical parameters, or any other factors. These results suggest that the acute or repeated-dose oral administration of crude antifungal compounds produced by Lb. plantarum AF1 plus Lb. plantarum HD1 is not toxic in male and female rats.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.150-150
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• 2003

Botulinum toxin type A was intramuscularly administered to Sprague-Dawley rats in both single and 28-day repeated dose toxicity studies. In the single dose toxicity study performed at 25, 50, 100, and 200 ng/kg, LD50 was estimated to be 70.71 ng/kg for males and 97.63 ng/kg for females.(omitted)

• Environmental Analysis Health and Toxicology
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• v.16 no.4
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• pp.211-221
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• 2001

The purpose of this study was to investigate the acute (4 hours) and repeated-dose (6 hours a day, 5 days a week, 4 weeks) toxic effects of 1-hexene on Sprague-Dawley (SD) rats which were treated by inhalation. The results were as follows; 1. The median lethal concentration(LC$_{50}$) was estimated 52,694 ppm (confidence limit 95％; 49,494~55,447 ppm) in acute inhalation. Abnormal clinical signs related to the 1-Hexene were not observed with the acute inhalation dose. Cross findings of necropsy revealed on evidence of specific toxicity related to the 1-hexene. II. By repeated inhalation exposure the body weight of male were more or less reduced by the dose of 2,500 ppm and 5,000 ppm compared with control group. However there were no significant variation hematology and blood biochemistry for the exposed rats compared with the control rats. Abnormal clinical signs and gross findings of necropsy related to the 1-hexene were not shown. In conclusion when we exposed 1-hexene to SD rats for 4 weeks, 5 days per week, 6 hours per day, the Lowest observed effect level (LOEL) was over 2,500 ppm and Non observed effect level (NOEL) was below 500 ppm.

• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.161-172
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• 1994

This study was conducted to examine DA-3002, a biosynthetic human growth hormone, for its acute and subacute toxicities in mice and rats. The drug was administered subcutaneously and orally at a dose level of 1.0, 3.0, 8.9, 26.7 or 80.0 lU/kg once for single dose toxicity and given subcutaneously at a dose level of 0.34, 1.7 or 8.4 lU/kg daily for 13 weeks to investigate repeated dose toxicity. In the acute toxicity study, doses up to 80 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal changes which could be attributed to toxic effect of DA-3002. In the subacute toxicity study, the growth hormone was tolerated well in broth mice and rats. No drug related deaths occurred and all animals appeared to be normal throughout the dosing period. Increases in body weight gain, food utilisation and absolute organ weights were observed in the rats in the high dose group. Mild changes in the blood chemical parameters were also seen in the treated groups. Histopathologically, however, no abnormal changes were observed in any organ. The changes noted during the treatment periods presumably represent exaggerated pharmacological effects of the growth hormone, and no observed adverse effect level (NOAEL) was considered to be more than 8.4 lu/kg/day.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.32 no.3
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• pp.209-220
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• 2022

Objectives: This study was performed to suggest how to re-establish criterion for toxic substances under the Chemical Control Act (CCA) in South Korea by comparing the GHS (Globally Harmonized System of Classification and Labeling of Chemicals) score and toxic properties. Methods: Toxic substances were classified into seven groups (Acute toxicity (1A), Chronic toxicity (2C), Environmental hazards (3E), Acute toxicity & chronic toxicity (4AC), Chronic toxicity & environmental hazards (5CE), Acute toxicity & environmental hazards (6AE), and Acute toxicity & chronic toxicity & environmental hazards (7ACE)) according to their toxic properties. The GHS score was calculated to sum up five toxicity indicators (health acute toxicity, health repeated toxicity, carcinogenicity, health other chronic toxicity and environmental hazards). Results: The GHS score of 7ACE was higher by 7 times that of 1A. 1A is the only group which has lower than the total GHS score. The highest score was 47, for sodium chromate (CAS no. 7775-11-3), which belongs to group 7ACE. This is classified as acute toxicity, carcinogenicity, germ cell mutagenicity, reproductive toxicity, and acute and chronic environmental hazard. On the other hand, the lowest score was 2.75, which was assigned to 177 chemicals belonging to group 1A. When the health acute toxicity indicator was omitted from the toxic criterion, toxic substances could be divided into the sub-groups 'human chronic hazards group' (HCG) and 'environmental hazards group' (EG) according to their GHS score and properties. Conclusions: The proposed criterion for toxic substances is to establish sub-groups defined as HCG and EG for separate control and that the 1A group be moved to substances requiring preparation for accidents under the CCA.

• The Korean Journal of Community Living Science
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• v.27 no.3
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• pp.437-449
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• 2016

To provide information on the safety of crude antifungal compounds produced by Bacillus subtilus SN7 isolated from Meju, we carried out an acute (single) oral dose toxicity test and 4 week repeated oral dose determination test on crude antifungal compounds in male and female Sprague Dawley rats. In the acute toxicity test, rats were treated with crude antifungal compounds produced by Bacillus subtilus SN7 orally at increasing dose levels (500, 1,000, and 2,000 mg/kg) and observed for 2 weeks. In the repeated-dose 28-day oral dose determination study, rats were orally administered doses of 500, 1,000, and 2,000 mg/kg daily for 4 weeks. There were no test article-related deaths or abnormal clinical signs in the two studies. In the 4 week repeated oral dose determination test, there were also no significant differences in clinical signs, body and organ weight changes, or any other hematological and biochemical parameters between the control and treated groups. The results suggest that the crude antifungal compounds produced by Bacillus subtilus SN7 up to a dosage level of 2,000 mg/kg are not toxic in male and female rats.

• Toxicological Research
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• v.13 no.3
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• pp.237-245
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• 1997

As the development of a pharmaceutical product is a dynamic process which involves continuousfeed-back between non-clinical and clinical studies, the integration of pharmacokinetics into toxicity testing became increasingly important in recent years. Toxicokinetic measurements in the toxicity studies is considered to be an important scientific approach in the interpretation of the toxicology findings and the promotion of rational study design development. Primarily this research project was conducted to determine the systemic exposure achieved in acute toxicity test and its relationship to dose level and the time course of the toxicity study. Acute hepatotoxicity study and its relevant toxicokinetic study in mice were performed using acetarninophen (AA) as a model compound. The correlation between acute hepatotoxicity indices and toxicokinetic parameters following intraperitoneally administration of various dosages of AA in mice was evaluated and discussed minutely in the text. Based on these studies, single-dose toxicity testing of AA including kinetic studies was evaluated in ICR mice for 7 days and interpreted in the text. Our results from the integration of toxicokinetic monitoring into single-dose toxicity study enable to elucidate the relation of the exposure achieved in toxicity study to toxicological findings and assist in the selection of appropriate dose levels for use in repeated-dose toxicity or later studies.

• Toxicological Research
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• v.35 no.3
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• pp.225-232
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• 2019

Thymus vulgaris L. is widely used as an ingredient in cooking and in herbal medicine. However, there is little information about its toxicity. The present study was performed to evaluate the acute and repeated 28-day oral dose toxicity of thyme essential oil in rats. For the acute toxicity test, two groups of three rats were used. The rats received a single dose of essential oil: 300 or 2,000 mg/kg of body weight (bw). The rats were observed individually during the first four hours, and then daily until day 14. For the toxicity test with repeated doses, four groups of 10 rats were used. Doses of 100, 250, and 500 mg/kg/day were tested for 28 days. At the end of the experiment, blood was collected and the animals were sacrificed. Histopathological examination showed that in the lungs of rats given the 2,000 mg/kg bw dose, polymorph nuclear infiltrates, hemosiderin macrophages, and interstitial space thickening were present. In the repeated dose study, all rats survived the 28-day treatment period and apparently showed no signs of toxicity. The hematological and biochemical parameters were not altered. The histopathological study of the organs showed severe changes in the lung, with the dose of 500 mg/kg/day; in the other organs, no alterations were observed or the changes were slight. The body weight was only altered in male rats given the 500 mg/kg dose. The relative weight of the organs did not show any significant changes. Our studies revealed that the essential oil of Thymus vulgaris has moderate oral toxicity according to the results of the acute test, whereas the results of the 28-day oral toxicity test suggest that the no-observed-adverse effect level (NOAEL) is greater than 250 mg/kg/day.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2003.10a
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• pp.150-150
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• 2003